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Author(s): Han, Claudia; Li, Rick; Hansen, Emily; Bennett, Hunter; Poirion, Olivier; Buchanan, Justin; Challacombe, Jean; Fixsen, Bethany; Trescott, Samantha; Schlachetzki, Johannes CM; Preissl, Sebastian; Wang, Allen; O’Connor, Carolyn; Warden, Anna; Shriram, Shreya; Kim, Roy; Nguyen, Celina; Schafer, Danielle; Ramirez, Gabriela; Anavim, Samuel; Johnson, Avalon; Sajti, Eniko; Gupta, Mihir; Levy, Michael; Ben-Haim, Sharona; Gonda, David; Laurent, Louise; Glass, Christopher; Coufal, Nicole | Abstract: The fetal period is a critical time for brain development, characterized by neurogenesis, neural migration, and synaptogenesis 1-3 . Microglia, the tissue resident macrophages of the brain, are observed as early as the fourth week of gestation 4 and are thought to engage in a variety of processes essential for brain development and homeostasis 5-11 . Conversely, microglia phenotypes are highly regulated by the brain environment 12-14 . Mechanisms by which human brain development influences the maturation of microglia and microglia potential contribution to neurodevelopmental disorders remain poorly understood. Here, we performed transcriptomic analysis of human fetal and postnatal microglia and corresponding cortical tissue to define age-specific brain environmental factors that may drive microglia phenotypes. Comparative analysis of open chromatin profiles using bulk and single-cell methods in conjunction with a new computational approach that integrates epigenomic and single-cell RNA-seq data allowed decoding of cellular heterogeneity with inference of subtype- and development stage-specific transcriptional regulators. Interrogation of in vivo and in vitro iPSC-derived microglia models provides evidence for roles of putative instructive signals and downstream gene regulatory networks which establish human-specific fetal and postnatal microglia gene expression programs and potentially contribute to neurodevelopmental disorders.

I. INTRODUCTION Victoria, a pregnant inmate housed in a Louisiana state prison, brought a civil rights action challenging the prison's policy of requiring her to obtain a court order to receive an elective abortion.1 Although Louisiana state law purported to allow Victoria to obtain an elective abortion, Victoria was unable to obtain her abortion because of procedural delays.2 Victoria was released from prison before she gave birth but her pregnancy was too far along for her to legally obtain an abortion. She was therefore forced to carry her pregnancy to term and forced to place her newborn child with adoptive parents.3 Had she given birth in prison, she would have been shackled to her hospital bed, as Louisiana policies require.4 Little information regarding pregnancy, prenatal care, perinatal outcomes, and access to elective abortions for female inmates exists. We know, however, that between six and ten percent of the women entering jail or prison are pregnant5 and that more women may become impregnated in prison as a result of rape by prison guards.6 Although not all pregnant inmates are incarcerated for the majority of their pregnancies, the majority of women who carry their pregnancies to term face inadequate prenatal care during their incarceration.7 Furthermore, due to factors such as poor socioeconomic conditions and drug use before incarceration, female inmates may have pregnancies with higher risk factors than the unincarcerated population.8 Carrying a pregnancy to term generally ends in a degrading and traumatic experience for the female inmate, such as shackling women during childbirth, which is the policy in federal prison and in almost all state prisons.9 Although shackling laws have recently come under attack by women's and human rights groups such as Amnesty International and the American Civil Liberties Union (the "ACLU"), only ten states have repealed these laws.10 The other forty states still use some type of restraint, including belly chains, leg irons, and handcuffs during labor and delivery." Shackling may cause complications during delivery such as hemorrhage or decreased fetal heart rate.12 The numerous health risks and emotional difficulties involved in carrying a pregnancy to term while incarcerated may give a female inmate strong motivation to seek an elective abortion. Currently, there is no clear national policy regarding access to elective abortions for pregnant inmates.13 The federal courts have split on the issue of whether female inmates have a right to elective abortions and disagree about what that right substantively entails.14 A national standard is necessary to protect pregnant inmates' rights to elective abortions. Given the current political climate, which is particularly hostile towards abortion rights, it is the United States Supreme Court that can most effectively accomplish the goal of establishing a clear national policy regarding the rights of female prisoners to have elective abortions. This Note will examine the likely outcome should the Supreme Court hear a case to resolve the current circuit split. In light of the Court's recent decisions relating to abortion rights under the Fourteenth Amendment in Planned Parenthood v. Casey and Gonzalez v. Carhart, the Court will likely rule that pregnant inmates must have meaningful access to elective abortions under the Fourteenth Amendment. The rationales expressed by the Sixth, Third, Fifth, and Eighth Circuits in deciding the relevant cases likewise suggest this result. The Court, however, will likely find that denying pregnant inmates access to elective abortions does not constitute cruel and unusual punishment under the Eighth Amendment. Part II of this Note provides a more extensive look at the facts relating to female inmates' access to elective abortions in federal and state prisons and why such access is particularly important to incarcerated women. Part III examines both federal and state policies regarding pregnant prisoners' access to elective abortions, which often deny female prisoners access to abortions, either constructively through procedural delays or explicitly through state laws that restrict access. …