The following is well known. Given a symmetric differential operator, like $\partial_x^2$, defined on smooth functions of compact support on $\mathbb{R}$, $C_0^\infty(\mathbb{R})$, one can count the number of independent $L^2$-normalizable solutions of $\partial_x\pm i$ and use the von Neumann index theorem to classify possible self-adjoint extensions of this operator on $L^2(\mathbb{R})$. This can be generalized to more complicated differential operators, to $\mathbb{R}^n$ as well as bounded open subsets thereof.

On the other hand, suppose that I have a manifold $M$ that is covered by a set of open charts $U_i$ with differential operators $D_i$ defined in corresponding local coordinates. It is easy to check if the $D_i$ are restrictions of a globally defined differential operator $D$ on $M$: the transition functions on intersections of charts $U_i\cap U_j$ must transform $D_i$ into $D_j$ and vice versa. Suppose that is the case and that I am interested in self-adjoint extensions of $D$ to $L^2(M)$ (supposing that an integration measure is given and that $D$ is symmetric with respect to it). Now, the question:

Is there way of classifying the self-adjoint extensions of $D$ on $L^2(M)$ in terms of its definition in local coordinates, the actions of $D_i$ on $C_0^\infty(U_i)$.

A simple example would be the cover of $S^1$ by two overlapping charts. I know that a self-adjoint extension of $\partial_x^2$ on $[0,1]$ with periodic boundary conditions gives the naturally defined self-adjoint Laplacian on $S^1$. Then $(0,1)$ is interpreted as a chart on $S^1$ that excludes one point. However, I don't know how to define the self-adjoint Laplacian on $S^1$ if it's given on two overlapping charts.